The purpose of these experiments is to evaluate the possibility of modifying the cytotoxic response of chemotherapeutic drugs with mildly toxic levels of photodynamic injury caused by hematoporphyrin and light. Tissue culture experiments using both growth and clonogenic assays of L1210 leukemia were used to measure effects. A paired control experimental design was important in the development of techniques for evaluating the combination of these two potentially lethal effects. Prolonged hematophoryrin incubation followed by standardized illumination and subsequent chemotherapeutic treatment inhibits both growth and clonogenic capacity of L1210 cells. Melphalan and Actinomycin-D dose response curves using the paired control experimental technique indicated that the toxicities of these drugs were reproducibly enhanced by prior mild photodynamic injury. However, the effects with Actinomycin-D were not as large as might have been expected from the enhancement of transport of Actinomycin-D by photodynamic injury reported by other laboratories.